This Center will continue its multidisciplinary approach to elucidate factors that play significant roles in the pathogenesis of atherosclerosis. A unique feature of our program is a strong emphasis on thrombosis as it relates to atherosclerotic diseases. Platelet adherence to cells, platelet and endothelial receptor sites for biologically active molecules, sialoproteins as they relate to surface phenomena, and the production of factor VIII by endothelial cells will be investigated. Bovine plasma factor VIII will be purified and characterized. Much of our basic investigations will be done with cells grown in Tissue culture systems. The growth, properties and structure of human endothelial cells will be examined. Endothelial cells cultured from cerebral vessels will be compared with those from other vascular beds. The extent to which the fatty acid composition of cultured human fibroblasts can be altered will be investigated, and the effects of these changes on membrane transport and the function of membrane-bound enzymes will be studied. Cholesterol flux and esterification relative to cell fatty acid saturation also will be determined. Studies of atherogenesis and regression in subhuman primates will be continued, with emphasis on the role of dietary disaccharides and the metabolism of collagen and elastin in the arterial wall. Clinical investigations will be carried out in both adult and pediatric populations. The latter are designed to assess the incidence and prevalence of hyperlipidemia, hypertension and obesity in a school age population and to examine certain genetic aspects of hyperlipidemia. Adult clinical studies involve the importance of circulating platelet aggregates, the composition of plasma lipoproteins in various types of hyperlipoproteinemia and the effect of reduction in plasma lipids on the lipid content of blood cells.